Bioactive fractions and compound of Ardisia crispa roots exhibit anti-arthritic properties mediated via angiogenesis inhibition in vitro

Abstract

Background Ardisia crispa (Thunb.) A.DC (Primulaceae), is a medicinal herb traditionally used by Asian people as remedies to cure inflammatory related diseases, including rheumatism. The plant roots possess various pharmacological activities including antipyretic, anti-inflammation and antitumor. Previous phytochemical studies of the plant roots have identified long chain alkyl-1,4-benzoquinones as major constituents, together with other phytochemicals. Hexane fraction of the plant roots (ACRH), was previously reported with anti-angiogenic and anti-arthritic properties, while its effect on their anti-arthritic in vitro, is yet unrevealed. Considering the significance of angiogenesis inhibition in developing new anti-arthritic agent, thus we investigated the anti-arthritic potential of Ardisia crispa roots by suppressing angiogenesis, in vitro. Methods Ardisia crispa roots hexane extract (ACRH) was prepared from the plant roots using absolute n-hexane. ACRH was fractionated into quinone-rich fraction (QRF) and further isolated to yield benzoquinonoid compound (BQ), respectively. In vitro experiments using VEGF-induced human umbilical vein endothelial cells (HUVECs) and IL-1β-induced human fibroblast-like synoviocytes for rheumatoid arthritis (HFLS-RA) were performed to evaluate the effects of these samples on VEGF-induced HUVECs proliferation and tube formation, and towards IL-1β-induced HFLS-RA proliferation, invasion, and apoptosis, respectively. Therapeutic concentrations (0.05, 0.5, and 5 μg/mL) tested in this study were predetermined based on the IC50 values obtained from the MTT assay. Results ACRH, QRF, and BQ exerted concentration-independent antiproliferative effects on VEGF-induced HUVECs and IL-1β-induced HFLS-RA, with IC50 values at 1.09 ± 0.18, 3.85 ± 0.26, and 1.34 ± 0.16 μg/mL in HUVECs; and 3.60 ± 1.38, 4.47 ± 0.34, and 1.09 ± 0.09 μg/mL in HFLS-RA, respectively. Anti-angiogenic properties of these samples were verified via significant inhibition on VEGF-induced HUVECs tube formation, in a concentration-independent manner. The invasiveness of IL-1β-induced HFLS-RA was also significantly inhibited in a concentration-independent manner by all samples. ACRH and BQ, but not QRF, significantly enhanced the apoptosis of IL-1β-induced HFLS-RA elicited at their highest concentration (5 μg/mL) (P < 0.05). Conclusions These findings highlight the bioactive fractions and compound from Ardisia crispa roots as potential anti-arthritic agents by inhibiting both HUVECs and HFLS-RA’s cellular functions in vitro, possibly mediated via their anti-angiogenic effects.

Review of Malaysian Medicinal Plants with Potential Anticancer Activity

“…Finally, Ardisia crispa from Primulaceae also known as Mata Ayam in Malay consists of quinone, wogonin, oroxylin A, wogonoside, baicalin, anwulignan, bergenin, β-sitosterol, and viminolol (Blin et al, 2021). Compound quinone in general is a cytotoxic agent with selective cytotoxicity against cancer cells (Blin et al, 2021). Natural quinones are classified as secondary metabolites of plants based on their aromatic carbon skeleton.…”

A 1, 4-benzoquinone derivative isolated from Ardisia crispa (Thunb.) A. DC. root suppresses angiogenesis via its angiogenic signaling cascades

“…To date, there have not been many studies on this compound, except for its inhibition of acute inflammation and hyperalgesia ( Roslida, 2004 ). We had previously reported multiple studies on the plant’s root hexane and its fractionated extracts enriched with this aforementioned compound, labelled as ACRH and QRF, respectively, including anti-inflammatory, anti-arthritic, antitumor promotion and antiangiogenic ( Roslida and Kim, 2008 , Roslida et al, 2009 , Lau et al, 2009 , Roslida et al, 2011 , Sulaiman et al, 2012 , Hamid et al, 2013 , Hamsin et al, 2013 , Hamsin et al, 2014 , Yeong et al, 2013 , Yeong et al, 2014 , Yeong et al, 2015 , Hamid et al, 2017 , Wen Jun et al, 2019 , Blin et al, 2021a , Blin et al, 2021b ), However, little was known about the principal bioactive compound in ACRH and QRF that might also be responsible for its antiangiogenic property and the possible pathway involved. Therefore, in the current study, we isolated the compound and tested it in various in vitro angiogenesis and in vivo zebrafish assays, as well as in elucidating the potential protein targets responsible for the antiangiogenic effect of AC2.…”

The complete chloroplast genome sequence of Ardisia crispa Thunb.

“… 2016 ; Blin et al. 2021 ). The root of A. crispa has primarily been used as traditional medicines for a long time by Asians (Yin et al.…”

“… 2019 ; Blin et al. 2021 ). The triterpenoid saponins inside of the A. crispa root may be the main components that exert cytotoxicity in the biological activities of anti-tumor (Yin et al.…”

“…For instance, it is widely used in Malaysia to treat diseases such as ever, pain, swelling, rheumatism, and blood circulation (Blin et al. 2021 ). As a kind of Chinese Traditional Medicine as well, the root of A. crispa is known as ‘Bai-Liang-Jin’ in China.…”